Clinical Implications of the Innate and Adaptive Immune Response to HBV and HCV
- First Online:
The tolerogenicity of the liver renders it vulnerable to hepatotrophic pathogens such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Both viruses have successfully co-evolved within the human host by evading and counteracting immune control. Inadequate cell culture and animal models have limited definitive characterization of the immunological mechanisms arbitrating virus and host co-existence. The clinical sequelae of chronic viral hepatitis such as cirrhosis and hepatocellular carcinoma are not directly mediated by the viruses but rather by hepatotoxic immunological mediators and cytokines. The pro-fibrotic T helper 2 (Th2) response promoted by this altered cytokine milieu is associated with viral persistence. In this chapter, the innate and adaptive immune response to acute and chronic HBV and HCV is reviewed with particular focus on its clinical implications.
KeywordsNatural killer cells T lymphocytes Pattern recognition receptors TRAIL
Papers of particular interest, published recently, have highlighted as: •• Of major importance
- 8.Wieland S, et al. Genomic analysis of early immune responses in patients with acute hepatitis B virus infection. Proc Natl Acad Sci U S A. 2004;101:66669–74.Google Scholar
- 9.Bertoletti A, Ferrari C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut. 2011. doi:10.1136/gutjnl-2011-301073. Epub ahead of print.
- 16.Yu S, et al. Hepatitis B virus polymerase inhibits RIG-1 and Toll-like receptor 3-mediated beta interferon induction in human hepatocytes through interference with interferon regulatory factor 3 activation and dampening of the interaction between TBK1/IKKepsilon and DDX3. J Gen Virol. 2010;91:2080–90.PubMedCrossRefGoogle Scholar
- 21.Shin EC et al. Virus-induced type 1 IFN stimulates generation of immunoprotesasomes at the site of infection. J Clin Invest. 116:3006–3014.Google Scholar
- 22.Kaplan DE et al. Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C. Gastroenterology. 132:654–666Google Scholar
- 28.Zhang Z, et al. Hypercytolytic activity of hepatic natural killer cells correlates with liver injury in chronic hepatitis B patients. Hepatology. 2011;53(3):730–85.Google Scholar
- 31.•• Jin Z, et al. Accelerated liver fibrosis in hepatitis b virus transgenic mice: involvement of natural killer T cells. Hepatology. 2011;53:219–29. This study showed that one of the potential immunopathogenic mechanisms contributing to liver fibrosis in HBV infection is through the induction of HSC activation by NKT cells.PubMedCrossRefGoogle Scholar
- 43.Peppa D et al. Blockade of Immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection. PLoS Pathog. 6(12):e1001227Google Scholar
- 49.•• Ahlenstiel G. Early changes in natural killer cell function indicate virologic response to interferon therapy for hepatitis C. Gastroenterology. 2011;141:1231–9. This is the first study to examine NK cell activation in both peripheral blood and liver at a very early time point after treatment initiation. This study also demonstrated that the effect of exogenous IFN-α on NK cell activation and TRAIL expression occurs very early.PubMedCrossRefGoogle Scholar
- 51.Suppiah V., et al. IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European cohort: A cross-sectional study. PLoS Med 8(9):e1001092Google Scholar